rs11088086

Variant names:

• chr21-28736843-C-A
• rs11088086
• ENST00000824757.1:n.57+35151G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-28736843-C-A
• chr21-28736843-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000824757.1(ENSG00000232855):​n.57+35151G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 150,960 control chromosomes in the GnomAD database, including 6,081 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6081 hom., cov: 31)
• Consequence: ENSG00000232855 ENST00000824757.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 1 publications found

Genes affected

ENSG00000232855 (HGNC:58104):

HEMK2 (HGNC:16021): (N-6 adenine-specific DNA methyltransferase 1) This gene encodes an N(6)-adenine-specific DNA methyltransferase. The encoded enzyme may be involved in the methylation of release factor I during translation termination. This enzyme is also involved in converting the arsenic metabolite monomethylarsonous acid to the less toxic dimethylarsonic acid. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Mar 2023]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEMK2	XR_007067787.1	n.936+85062G>T		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000232855	ENST00000824757.1	n.57+35151G>T		intron_variant	Intron 1 of 8
ENSG00000232855	ENST00000824758.1	n.147+35151G>T		intron_variant	Intron 1 of 11
ENSG00000232855	ENST00000824759.1	n.139+35151G>T		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41392 AN: 150882 Hom.: 6068 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41450 AN: 150960 Hom.: 6081 Cov.: 31 AF XY: 0.271 AC XY: 19962 AN XY: 73662

African (AFR) AF: 0.332 AC: 13642 AN: 41058

American (AMR) AF: 0.324 AC: 4919 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.526 AC: 2698 AN: 5128

South Asian (SAS) AF: 0.153 AC: 730 AN: 4784

European-Finnish (FIN) AF: 0.149 AC: 1518 AN: 10212

Middle Eastern (MID) AF: 0.338 AC: 98 AN: 290

European-Non Finnish (NFE) AF: 0.239 AC: 16179 AN: 67822

Other (OTH) AF: 0.301 AC: 631 AN: 2094

Alfa AF: 0.254 Hom.: 7545

Bravo AF: 0.295

Asia WGS AF: 0.324 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11088086; hg19: chr21-30109165;